Selected Derivatives of Erythromycin B- and Anti-Malarial Studies.

Erythromycin A is an established anti-bacterial agent against Gram-positive bacteria, but it is unstable to acid. This led to an evaluation of erythromycin B and its derivatives because these have improved acid stability. These compounds were investigated for their anti-malarial activities, by their molecular docking into segments of the exit tunnel of the apicoplast ribosome from . This is believed to be the target of the erythromycin A derivative, azithromycin, which has mild anti-malarial activity. The erythromycin B derivatives were evaluated on the multi-drug (chloroquine, pyrimethamine, and sulfadoxine)-resistant strain K1 of for asexual growth inhibition on asynchronous culture. The erythromycin B derivatives were identified as active in vitro inhibitors of asexual growth of with low micro-molar IC values after a 72 h cycle. 5-Desosaminyl erythronolide B ethyl succinate showed low IC of 68.6 µM, -erythromycin B 86.8 µM, and erythromycin B 9-oxime 146.0 µM on the multi-drug-resistant K1 of . Based on the molecular docking, it seems that a small number of favourable interactions or the presence of unfavourable interactions of investigated derivatives of erythromycin B with constructed segment from the exit tunnel from the apicoplast of . is the reason for their weak in vitro anti-malarial activities.